tbuckley/cabot-search huggingface dataset:
Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening, and osteopontin release in abdominal aortic aneurysm
Authors: Markus U Wagenhäuser, Joscha Mulorz, Kim J Krott, Agnes Bosbach, Tobias Feige, Yae H Rhee, Madhumita Chatterjee, Niklas Petzold, Christopher Böddeker, Wiebke Ibing, Irena Krüger, Ana M Popovic, Ann Roseman, Joshua M Spin, Philip S Tsao, Hubert Schelzig, Margitta Elvers
Journal: Cardiovascular Research (2023)

Abdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases, but their role in AAA is poorly understood.
Global consensus process to establish a core dataset for hidradenitis suppurativa registries
Authors: Hannah E Wainman, Nisha S Chandran, John W Frew, Amit Garg, Angela Gibbons, Athena Gierbolini, Barbara Horvath, Gregor B Jemec, Brian Kirby, Joselyn Kirby, Michelle A Lowes, Antonio Martorell, Barry M McGrath, Haley B Naik, Hazel H Oon, Errol Prens, Christopher J Sayed, Linnea Thorlacius, Hessel H Van der Zee, Bente Villumsen, John R Ingram
Journal: British Journal of Dermatology (2023)

Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate.
Impact of ACCELERATE Paediatric Strategy Forums: a review of the value of multi-stakeholder meetings in oncology drug development
Authors: Andrew D J Pearson, Teresa de Rojas, Dominik Karres, Gregory Reaman, Nicole Scobie, Elizabeth Fox, Giovanni Lesa, Franca Ligas, Koen Norga, Karsten Nysom, Alberto Pappo, Brenda Weigel, Susan L Weiner, Gilles Vassal
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract In a landscape of an increasing number of products and histology and age agnostic trials for rare patient cancer, prioritization of products is required. Paediatric Strategy Forums, organized by ACCELERATE and the European Medicines Agency with participation of the US Food and Drug Administration, are multi-stakeholder meetings that share information to best inform pediatric drug development strategies and subsequent clinical trial decisions. Academia, industry, regulators, and patient advocates are equal members, with patient advocates highlighting unmet needs of children and adolescents with cancer. The 11 Paediatric Strategy Forums since 2017 have made specific and general conclusions to accelerate drug development. Conclusions on product prioritization meetings, as well as global master protocols, have been outputs of these meetings. Forums have provided information for regulatory discussions and decisions by industry to facilitate development of high-priority products; for example, 62% of high-priority assets (agreed at a Forum) in contrast to 5% of those assets not considered high priority have been the subject of a Paediatric Investigational Plan or Written Request. Where there are multiple products of the same class, Forums have recommended a focused and sequential approach. Class prioritization resulted in an increase in waivers for non-prioritized B-cell products (44% to 75%) and a decrease in monotherapy trials, proposed in Paediatric Investigation Plans (PIP) submissions of checkpoint inhibitors from 53% to 19%. Strategy Forums could play a role in defining unmet medical needs. Multi-stakeholder forums, such as the Paediatric Strategy Forum, serve as a model to improve collaboration in the oncology drug development paradigm.
Remodeling of intestinal epithelium derived extracellular vesicles by nanoparticles and its bioeffect on tumor cell migration
Authors: Yuxing Lin, Hailiang Deng, Feiyang Deng, Siyu Yao, Xinxin Deng, Yuxi Cheng, Ying Chen, Bing He, Wenbing Dai, Hua Zhang, Qiang Zhang, Xueqing Wang
Journal: Journal of Controlled Release (2023)
Repurposing nucleoside reverse transcriptase inhibitors (NRTIs) to slow aging
Authors: Thomas Brochard, Rebecca L. McIntyre, Riekelt H. Houtkooper, Andrei Seluanov, Vera Gorbunova, Georges E. Janssens
Journal: Ageing Research Reviews (2023)

Repurposing drugs already approved in the clinic to be used off-label as geroprotectors, compounds that combat mechanisms of aging, are a promising way to rapidly reduce age-related disease incidence in society. Several recent studies have found that a class of drugs-nucleoside reverse transcriptase inhibitors (NRTIs)-originally developed as treatments for cancers and human immunodeficiency virus (HIV) infection, could be repurposed to slow the aging process. Interestingly, these studies propose complementary mechanisms that target multiple hallmarks of aging. At the molecular level, NRTIs repress LINE-1 elements, reducing DNA damage, benefiting the hallmark of aging of 'Genomic Instability'. At the organellar level, NRTIs inhibit mitochondrial translation, activate ATF-4, suppress cytosolic translation, and extend lifespan in worms in a manner related to the 'Loss of Proteostasis' hallmark of aging. Meanwhile, at the cellular level, NRTIs inhibit the P2X7-mediated activation of the inflammasome, reducing inflammation and improving the hallmark of aging of 'Altered Intercellular Communication'. Future development of NRTIs for human aging health will need to balance out toxic side effects with the beneficial effects, which may occur in part through hormesis.
On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?
Authors: Lucia Scisciola, Fabiola Olivieri, Concetta Ambrosino, Michelangela Barbieri, Maria Rosaria Rizzo, Giuseppe Paolisso
Journal: Ageing Research Reviews (2023)

Here we propose that SGLT2 inhibitors (SGLT2i), a class of drugs primarily used to treat type 2 diabetes, could also be repositioned as anti-aging senomorphic drugs (agents that prevent the extrinsic harmful effects of senescent cells). As observed for metformin, another anti-diabetic drug with established anti-aging potential, increasing evidence suggests that SGLT2i can modulate some relevant pathways associated with the aging process, such as free radical production, cellular energy regulation through AMP-activated protein kinase (AMPK), autophagy, and the activation of nuclear factor (NF)-kB/inflammasome. Some interesting pro-healthy effects were also observed on human microbiota. All these mechanisms converge on fueling a systemic proinflammatory condition called inflammaging, now recognized as the main risk factor for accelerated aging and increased risk of age-related disease development and progression. Inflammaging can be worsened by cellular senescence and immunosenescence, which contributes to the increased burden of senescent cells during aging, perpetuating the proinflammatory condition. Interestingly, increasing evidence suggested the direct effects of SGLT-2i against senescent cells, chronic activation of immune cells, and metabolic alterations induced by overnutrition (meta-inflammation). In this framework, we analyzed and discussed the multifaceted impact of SGLT2i, compared with metformin effects, as a potential anti-aging drug beyond diabetes management. Despite promising results in experimental studies, rigorous investigations with well-designed cellular and clinical investigations will need to validate SGLT2 inhibitors' anti-aging effects.
Vagus nerve dysfunction in the post–COVID-19 condition: a pilot cross-sectional study
Authors: Gemma Lladós, Marta Massanella, Roser Coll-Fernández, Raúl Rodríguez, Electra Hernández, Giuseppe Lucente, Cristina López, Cora Loste, José Ramón Santos, Sergio España-Cueto, Maria Nevot, Francisco Muñoz-López, Sandra Silva-Arrieta, Christian Brander, Maria José Durà, Patricia Cuadras, Jordi Bechini, Montserrat Tenesa, Alicia Martinez-Piñeiro, Cristina Herrero, Anna Chamorro, Anna Garcia, Eulalia Grau, Bonaventura Clotet, Roger Paredes, Lourdes Mateu, Muñoz-Moreno José, Rodríguez-Fumaz Carmina, Prats Anna, Estany Carla, Vallejo Nuria, Villuendas Roger, Aranyó Julia, Marín Toni, Mitjans Julia, Casafont Ivette
Journal: Clinical Microbiology and Infection (2023)

The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints.
Incidentally Detected Lung Cancer in Persons Too Young or Too Old for Lung Cancer Screening in a Mississippi Delta Cohort
Authors: Wei Liao, Carrie Fehnel, Jordan Goss, Catherine J. Shepherd, Talat Qureshi, Anberitha T. Matthews, Meredith A. Ray, Nicholas R. Faris, Paul F. Pinsky, Matthew P. Smeltzer, Raymond U. Osarogiagbon
Journal: Journal of Thoracic Oncology (2023)
Merkel cell carcinoma recurrence risk estimation is improved by integrating factors beyond cancer stage: A multivariable model and web-based calculator
Authors: Aubriana M. McEvoy, Daniel S. Hippe, Kristina Lachance, Song Park, Kelsey Cahill, Mary Redman, Ted Gooley, Michael W. Kattan, Paul Nghiem
Journal: Journal of the American Academy of Dermatology (2023)
WarpDrive: Improving spatial normalization using manual refinements
Authors: Simón Oxenford, Ana Sofía Ríos, Barbara Hollunder, Clemens Neudorfer, Alexandre Boutet, Gavin J.B. Elias, Jurgen Germann, Aaron Loh, Wissam Deeb, Bryan Salvato, Leonardo Almeida, Kelly D. Foote, Robert Amaral, Paul B. Rosenberg, David F. Tang-Wai, David A. Wolk, Anna D. Burke, Marwan N. Sabbagh, Stephen Salloway, M. Mallar Chakravarty, Gwenn S. Smith, Constantine G. Lyketsos, Michael S. Okun, William S. Anderson, Zoltan Mari, Francisco A. Ponce, Andres Lozano, Wolf-Julian Neumann, Bassam Al-Fatly, Andreas Horn
Journal: Medical Image Analysis (2023)

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration. We show that the tool applied in a cohort of patients with Alzheimer's disease who underwent deep brain stimulation surgery helps create more accurate representations of the data as well as meaningful models to explain patient outcomes. The tool is built to handle any type of 3D imaging data, also allowing refinements in high-resolution imaging, including histology and multiple modalities to precisely aggregate multiple data sources together.
Redox-sensitive high-mobility group box-1 isoforms contribute to liver fibrosis progression and resolution in mice
Authors: Xiaodong Ge, Romain Desert, Fernando Magdaleno, Hui Han, Zhuolun Song, Sukanta Das, Dipti Athavale, Wei Chen, Ines Barahona, Daniel Lantvit, Hui Chen, Sunil Hwang, Natalia Nieto
Journal: Journal of Hepatology (2023)
FiCRoN, a deep learning-based algorithm for the automatic determination of intracellular parasite burden from fluorescence microscopy images
Authors: Graciela Juez-Castillo, Brayan Valencia-Vidal, Lina M. Orrego, María Cabello-Donayre, Laura Montosa-Hidalgo, José M. Pérez-Victoria
Journal: Medical Image Analysis (2023)
Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche
Authors: Huijuan Chen, Anzhi Hu, Mengdi Xiao, Shiyi Hong, Jing Liang, Quanlong Zhang, Yang Xiong, Mancang Gu, Chaofeng Mu
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches. Precise regulation of these cell types can remodel niches and develop new therapeutics. Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively. However, the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown, and there is no method available for predicting delivery efficiency in these cell types. Here, we constructed a three-dimensional bone marrow niche composed of three crucial cell populations: endothelial cells (ECs), mesenchymal stromal cells (MSCs), and osteoblasts (OBs). Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro. Less than 5% of nanocarriers were taken up by three stromal cell types, and most of them were located in the extracellular matrix. Delivery efficiency in sinusoidal ECs, arteriole ECs, MSCs, and OBs in vivo was analyzed. The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo. The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs, no matter what kind of nanocarrier. The overall efficiency into sinusoidal ECs was greatly lower than that into arteriole ECs. All nanocarriers were hard to be delivered into OBs (<1%). Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro. This study provided the methodology for niche-directed nanotherapeutics development.
Where is VALDO? VAscular Lesions Detection and segmentatiOn challenge at MICCAI 2021
Authors: Carole H. Sudre, Kimberlin Van Wijnen, Florian Dubost, Hieab Adams, David Atkinson, Frederik Barkhof, Mahlet A. Birhanu, Esther E. Bron, Robin Camarasa, Nish Chaturvedi, Yuan Chen, Zihao Chen, Shuai Chen, Qi Dou, Tavia Evans, Ivan Ezhov, Haojun Gao, Marta Girones Sanguesa, Juan Domingo Gispert, Beatriz Gomez Anson, Alun D. Hughes, M. Arfan Ikram, Silvia Ingala, H. Rolf Jaeger, Florian Kofler, Hugo J. Kuijf, Denis Kutnar, Minho Lee, Bo Li, Luigi Lorenzini, Bjoern Menze, Jose Luis Molinuevo, Yiwei Pan, Elodie Puybareau, Rafael Rehwald, Ruisheng Su, Pengcheng Shi, Lorna Smith, Therese Tillin, Guillaume Tochon, Hélène Urien, Bas H.M. van der Velden, Isabelle F. van der Velpen, Benedikt Wiestler, Frank J. Wolters, Pinar Yilmaz, Marius de Groot, Meike W. Vernooij, Marleen de Bruijne
Journal: Medical Image Analysis (2023)

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1 - EPVS, 9 for Task 2 - Microbleeds and 6 for Task 3 - Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1 - EPVS and Task 2 - Microbleeds and not practically useful results yet for Task 3 - Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.
Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy
Authors: Cristina Faldetta, Shaniko Kaleci, Johanna Chester, Cristel Ruini, Silvana Ciardo, Marco Manfredini, Stefania Guida, Camilla Chello, Carmen Cantisani, Jade N. Young, Patricia Cabral, Nicholas Gulati, Emma Guttman-Yassky, Giovanni Pellacani, Francesca Farnetani
Journal: Journal of the American Academy of Dermatology (2023)

Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described.
Wildlife endogenous retroviruses: colonization, consequences, and cooption
Authors: Patric Jern, Alex D. Greenwood
Journal: Trends in Genetics (2023)

Endogenous retroviruses (ERVs) are inherited genomic remains of past germline retroviral infections. Research on human ERVs has focused on medical implications of their dysregulation on various diseases. However, recent studies incorporating wildlife are yielding remarkable perspectives on long-term retrovirus–host interactions. These initial forays into broader taxonomic analysis, including sequencing of multiple individuals per species, show the incredible plasticity and variation of ERVs within and among wildlife species. This demonstrates that stochastic processes govern much of the vertebrate genome. In this review, we elaborate on discoveries pertaining to wildlife ERV origins and evolution, genome colonization, and consequences for host biology.
Co-delivery of drugs by adhesive transdermal patches equipped with dissolving microneedles for the treatment of rheumatoid arthritis
Authors: Lijie Zheng, Yuanzheng Chen, Xun Gu, Yingying Li, Hanqing Zhao, Wenjun Shao, Tao Ma, Chuanbin Wu, Qingqing Wang
Journal: Journal of Controlled Release (2023)
Unraveling the Unusual Subgenomic Organization in the Neopolyploid Free-Living Flatworm <i>Macrostomum lignano</i>
Authors: Kira S Zadesenets, Nikita I Ershov, Natalia P Bondar, Nikolai B Rubtsov
Journal: Molecular Biology and Evolution (2023)

Whole genome duplication (WGD) is an evolutionary event resulting in a redundancy of genetic material. Different mechanisms of WGD, allo- or autopolyploidization, lead to distinct evolutionary trajectories of newly formed polyploids. Genome studies on such species are important for understanding the early stages of genome evolution. However, assembling neopolyploid is a challenging task due to the presence of 2 homologous (or homeologous) chromosome sets and therefore the existence of the extended paralogous regions in its genome. Post-WGD evolution of polyploids includes cytogenetic diploidization leading to the formation of species, whose polyploid origin might be hidden by disomic inheritance. Earlier we uncovered the hidden polyploid origin of the free-living flatworms of the genus Macrostomum (Macrostomum lignano, M. janickei, and M. mirumnovem). Cytogenetic diploidization in these species is accompanied by intensive chromosomal rearrangements including chromosomes fusions. In this study, we unravel the M. lignano genome organization through generation and sequencing of 2 sublines of the commonly used inbred line of M. lignano (called DV1) differing only in a copy number of the largest chromosome (MLI1). Using nontrivial assembly free comparative analysis of their genomes, we deciphered DNA sequences belonging to MLI1 and validated them by sequencing the pool of microdissected MLI1. Here we presented the uncommon mechanism of genome rediplodization of M. lignano, which consists of (i) presence of 3 subgenomes, which emerged via formation of large fused chromosomes and its variants, and (ii) sustaining their heterozygosity through inter- and intrachromosomal rearrangements.
GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma
Authors: Christoph Neumayer, Denise Ng, David Requena, Caroline S Jiang, Adam Qureshi, Roger Vaughan, Thazha P Prakash, Alexey Revenko, Sanford M Simon
Journal: Molecular Therapy (2023)

Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer caused by a dominant recurrent fusion of the heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PRKACA). Current therapies such as chemotherapy and radiation have limited efficacy, and new treatment options are needed urgently. We have previously shown that FLC tumors are dependent on the fusion kinase DNAJB1::PRKACA, making the oncokinase an ideal drug target. mRNA degrading modalities such as antisense oligonucleotides or small interfering RNAs (siRNAs) provide an opportunity to specifically target the fusion junction. Here, we identify a potent and specific siRNA that inhibits DNAJB1::PRKACA expression. We found expression of the asialoglycoprotein receptor in FLC to be maintained at sufficient levels to effectively deliver siRNA conjugated to the GalNAc ligand. We observe productive uptake and siRNA activity in FLC patient-derived xenografts (PDX) models in vitro and in vivo. Knockdown of DNAJB1::PRKACA results in durable growth inhibition of FLC PDX in vivo with no detectable toxicities. Our results suggest that this approach could be a treatment option for FLC patients.
How do successive vaccinations and SARS-CoV-2 infections impact humoral immunity dynamics: An 18-month longitudinal study
Authors: A.N. Diep, J. Schyns, C. Gourzones, E. Goffin, I. Papadopoulos, S. Moges, F. Minner, O. Ek, G. Bonhomme, M. Paridans, N. Gillain, E. Husson, M. Garigliany, G. Darcis, C. Saegerman, D. Desmecht, M. Guillaume, Donneau A.F., F. Bureau, L. Gillet
Journal: Journal of Infection (2023)
A modified closure method during endoscopic full-thickness resection for a gastrointestinal stromal tumor: “neck” clipping and cutting
Authors: Zeliang Yang, Yuting Jiang, Yangyang Chen, Jie Yang, Xiaoling Zheng
Journal: Endoscopy (2023)

Endoscopic full-thickness resection (EFTR) is a surgical approach to effectively resect gastrointestinal stromal tumors (GISTs) that originate from the intrinsic muscular layer and grow in a convex fashion toward the peritoneal cavity. Because of the intentional perforation formed by EFTR, the patient's prognosis is closely related to preventing gastrointestinal contents entering the extraluminal space. In pursuit of the most effective closure methods, different endoscopic closure techniques are therefore being developed. An endoscopic closure method was first developed by Zhou et al. using metal clips to close the post-EFTR defect, which was later developed with the endoloop-assisted closure method, and finally emerged as various methods including the over-the-scope (OTS) clip method [1], all with the ultimate goal of pursuing the fastest closure to prevent the passage of gastrointestinal contents and ultimately improve the patient's prognosis.
Effective management of a retropharyngeal abscess using endoscopic complete-layer resection and drainage
Authors: Xu Shan, Zhang Tao, Tao Kong, Jie Liu, Qingyu Zeng
Journal: Endoscopy (2023)

Retropharyngeal abscess, a rare complication of foreign body ingestion that is usually associated with trauma to the retropharyngeal wall [1] [2], is also a life-threatening medical and surgical emergency, which usually requires incision and drainage [3]. Foreign bodies such as fish bones are the most common traumatic cause of retropharyngeal abscess [4]. We present a case to illustrate endoscopic complete-layer resection with drainage as a safe and effective method of treating retropharyngeal abscesses.